Trial Outcomes & Findings for A Phase 1/2, Open-Label, Dose-Escalation Study of JI-101, in Patients With Advanced Solid Tumors (NCT NCT00842335)

NCT ID: NCT00842335

Last Updated: 2013-06-24

Results Overview

The primary objective of this study was to determine the maximum tolerated dose (MTD) of JI-101 when administered orally in patients with advanced solid tumors. The MTD was established based on safety data from Cycle 1. Patients who completed 21 days of treatment in Cycle 1 were considered to have completed the study for the determination of MTD. Patients were eligible to continue treatment with JI-101 until they experienced disease progression or unacceptable treatment-related toxicity. Unacceptable treatment-related toxicity was defined as a clinically significant AE or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications, and that was attributed to JI 101.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 18 participants
• Primary outcome timeframe: 28 days (1 cycle)
• Results posted on: 2013-06-24

Participant Flow

This study was conducted at one clinical site in the US. First Patient Enrolled: 24 February 2009 Cut-off Date: 15 February 2011

Participant milestones

Measure	JI-101 JI-101 : JI-101, 50 mg capsules, will be administered daily for up to 112 days (four 28-day cycles); treatment may be extended if, in the opinion of the investigator, a patient has tolerated the treatment and appears to be benefitting from receiving study medication
Overall Study STARTED	18
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase 1/2, Open-Label, Dose-Escalation Study of JI-101, in Patients With Advanced Solid Tumors

Baseline characteristics by cohort

Measure	JI-101 n=18 Participants JI-101 : JI-101, 50 mg capsules, will be administered daily for up to 112 days (four 28-day cycles); treatment may be extended if, in the opinion of the investigator, a patient has tolerated the treatment and appears to be benefitting from receiving study medication
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants
Age Continuous	59.8 years STANDARD_DEVIATION 9.11 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants

PRIMARY outcome

Timeframe: 28 days (1 cycle)

Population: Full Analysis Population (FAS) or Modified Intent-to-Treat (mITT) Population: All patients enrolled into the study who received JI-101 and completed at least 21 days of dosing in Cycle 1 comprised the FAS. Safety Population: Included all patients who received at least one dose of study drug. This population was used for all safety analyses.

The primary objective of this study was to determine the maximum tolerated dose (MTD) of JI-101 when administered orally in patients with advanced solid tumors.

The MTD was established based on safety data from Cycle 1. Patients who completed 21 days of treatment in Cycle 1 were considered to have completed the study for the determination of MTD.

Patients were eligible to continue treatment with JI-101 until they experienced disease progression or unacceptable treatment-related toxicity. Unacceptable treatment-related toxicity was defined as a clinically significant AE or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications, and that was attributed to JI 101.

Outcome measures

Measure	JI-101 n=18 Participants JI-101 : JI-101, 50 mg capsules, will be administered daily for up to 112 days (four 28-day cycles); treatment may be extended if, in the opinion of the investigator, a patient has tolerated the treatment and appears to be benefitting from receiving study medication
Maximum Tolerated Dose (MTD) of JI-101	400 mg

SECONDARY outcome

Timeframe: Up to 112 days (up to four 28-day cycles) or longer if the patient is benefiting from treatment

Population: Only one subject withdrew due to an adverse event.

Number of participants withdrawn from study due to adverse events

Outcome measures

Measure	JI-101 n=18 Participants JI-101 : JI-101, 50 mg capsules, will be administered daily for up to 112 days (four 28-day cycles); treatment may be extended if, in the opinion of the investigator, a patient has tolerated the treatment and appears to be benefitting from receiving study medication
Number of Participants Reaching Maximum Tolerated Dose	18 participants

SECONDARY outcome

Timeframe: Up to 112 days ( four 28-day cycles)

Population: All 18 participants were analyzed.

Stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started.

Progressive disease: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions

Outcome measures

Measure	JI-101 n=18 Participants JI-101 : JI-101, 50 mg capsules, will be administered daily for up to 112 days (four 28-day cycles); treatment may be extended if, in the opinion of the investigator, a patient has tolerated the treatment and appears to be benefitting from receiving study medication
Overall Clinical Response by Cycle Cycle 10 - Progressive Disease	1 participants
Overall Clinical Response by Cycle Cycle 12 - Progressive Disease	0 participants
Overall Clinical Response by Cycle Cycle 2 - Stable Disease	7 participants
Overall Clinical Response by Cycle Cycle 2 - Progressive Disease	10 participants
Overall Clinical Response by Cycle Cycle 4 - Stable Disease	5 participants
Overall Clinical Response by Cycle Cycle 4 - Progressive Disease	2 participants
Overall Clinical Response by Cycle Cycle 6 - Stable Disease	5 participants
Overall Clinical Response by Cycle Cycle 6 - Progressive Disease	0 participants
Overall Clinical Response by Cycle Cycle 8 - Stable Disease	3 participants
Overall Clinical Response by Cycle Cycle 8 - Progressive Disease	2 participants
Overall Clinical Response by Cycle Cycle 10 - Stable Disease	2 participants
Overall Clinical Response by Cycle Cycle 12 - Stable Disease	2 participants
Overall Clinical Response by Cycle Cycle 14 - Stable Disease	1 participants
Overall Clinical Response by Cycle Cycle 14 - Progressive Disease	0 participants
Overall Clinical Response by Cycle Cycle 16 - Stable Disease	1 participants
Overall Clinical Response by Cycle Cycle 16 - Progressive Disease	0 participants

SECONDARY outcome

Timeframe: Up to 112 days (four 28-day cycles) or longer if the patient is benefiting from treatment

Population: The efficacy analyses were performed using all patients, who had at least one post-treatment evaluation for tumor assessment (N=17). The overall response was based on the number of cycles of treatment before the participant experienced progressive disease.

Progression: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions

Outcome measures

Measure	JI-101 n=17 Participants JI-101 : JI-101, 50 mg capsules, will be administered daily for up to 112 days (four 28-day cycles); treatment may be extended if, in the opinion of the investigator, a patient has tolerated the treatment and appears to be benefitting from receiving study medication
Days to Progression	55 days Interval 19.0 to 444.0

Adverse Events

JI-101

Serious events: 6 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	JI-101 n=18 participants at risk Maximum tolerated dose
Respiratory, thoracic and mediastinal disorders dyspnea	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Infections and infestations pneumonia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders peritonitis	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) metastases to central nervous system	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders pathological fracture	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders duodenal obstruction	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders impaired gastric emptying	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders diarrhea	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Infections and infestations urinary tract infection	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Nervous system disorders subarachnoid hemorrhage	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders dyspnea exertional	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.

Other adverse events

Measure	JI-101 n=18 participants at risk Maximum tolerated dose
Blood and lymphatic system disorders Anemia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Blood and lymphatic system disorders Lymphadenopathy	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Blood and lymphatic system disorders Lymph node pain	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Blood and lymphatic system disorders Neutropenia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Blood and lymphatic system disorders Thrombocytopenia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Ear and labyrinth disorders Ear discomfort	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Ear and labyrinth disorders Ear disorder	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Ear and labyrinth disorders Ear pain	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Ear and labyrinth disorders Hyperacusis	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Ear and labyrinth disorders Tinnitus	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Endocrine disorders Hypothyroidism	22.2% 4/18 • Number of events 4 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Eye disorders Acquired corneal dystrophy	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Eye disorders Dellen	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Eye disorders Diplopia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Eye disorders Dry eye	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Eye disorders Eye pain	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Eye disorders Intraocular pressure increased	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Eye disorders Macular degeneration	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Eye disorders Pseudoexfoliation of lens capsule	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Eye disorders Vision blurred	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Eye disorders Visual acuity reduced	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Cardiac disorders Tachycardia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Abdominal distension	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Abdominal pain	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Abdominal tenderness	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Aphthous stomatitis	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Ascites	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Constipation	33.3% 6/18 • Number of events 6 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Diarrhea	27.8% 5/18 • Number of events 5 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Dry mouth	22.2% 4/18 • Number of events 4 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Dyspepsia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Eructation	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Flatulence	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Frequent bowel movements	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Gastroesophageal reflux disease	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Glossodynia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Hematochezia	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Nausea	50.0% 9/18 • Number of events 9 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Oral pain	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Pyrexia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Retching	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Stomatitis	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Tongue blistering	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Gastrointestinal disorders Vomiting	38.9% 7/18 • Number of events 7 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Asthenia	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Chills	27.8% 5/18 • Number of events 5 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Edema peripheral	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Fatigue	61.1% 11/18 • Number of events 11 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Feeling cold	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Gait disturbance	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Influenza like illness	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Mass	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Non-cardiac chest pain	22.2% 4/18 • Number of events 4 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Pain	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Pyrexia	22.2% 4/18 • Number of events 4 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Temperature intolerance	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
General disorders Thirst	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Hepatobiliary disorders Hyperbilirubinemia	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Infections and infestations Clostridial infection	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Infections and infestations Fungal infection	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Infections and infestations Furuncle	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Infections and infestations Nasal abscess	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Infections and infestations Upper respiratory tract infection	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Infections and infestations Urinary tract infection	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Infections and infestations Vaginal abscess	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Infections and infestations Vaginal infection	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Infections and infestations Vulvovaginal mycotic infection	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Activated partial thromboplastin time prolonged	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Alanine aminotransferase increased	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Aspartate aminotransferase increased	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood alkaline phosphatase increased	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood amylase decreased	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood bilirubin increased	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood calcium decreased	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood chloride decreased	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood cortisol decreased	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood creatinine decreased	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood creatinine increased	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood glucose increased	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood potassium increased	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood pressure orthostatic	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood sodium decreased	22.2% 4/18 • Number of events 4 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Blood uric acid increased	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Carbon dioxide decreased	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations International normalized ratio increased	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Investigations Weight decreased	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Metabolism and nutrition disorders Anorexia	72.2% 13/18 • Number of events 13 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Metabolism and nutrition disorders Dehydration	38.9% 7/18 • Number of events 7 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Metabolism and nutrition disorders Hyperglycemia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Metabolism and nutrition disorders Hyperkalemia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Metabolism and nutrition disorders Hypoalbuminemia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Metabolism and nutrition disorders Hypocalcemia	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Metabolism and nutrition disorders Hyponatremia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Metabolism and nutrition disorders Hypokalemia	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Arthritis	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Back pain	27.8% 5/18 • Number of events 5 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Joint swelling	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Muscle spasms	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Myalgia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Neck pain	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Pain in jaw	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Sensation of heaviness	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Shoulder pain	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Musculoskeletal and connective tissue disorders Temporomandibular joint syndrome	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Keratoacanthoma	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Nervous system disorders Balance disorder	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Nervous system disorders Dizziness	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Nervous system disorders Dysgeusia	27.8% 5/18 • Number of events 5 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Nervous system disorders Headache	27.8% 5/18 • Number of events 5 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Nervous system disorders Hyperesthesia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Nervous system disorders Hypoesthesia	22.2% 4/18 • Number of events 4 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Nervous system disorders Migraine	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Psychiatric disorders Abnormal dreams	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Psychiatric disorders Anxiety	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Psychiatric disorders Depression	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Psychiatric disorders Insomnia	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Psychiatric disorders Nightmare	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Renal and urinary disorders Dysuria	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Renal and urinary disorders Hematuria	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Renal and urinary disorders Incontinence	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Renal and urinary disorders Micturition disorder	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Renal and urinary disorders Micturition urgency	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Renal and urinary disorders Nocturia	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Renal and urinary disorders Pollakiuria	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Renal and urinary disorders Proteinuria	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Renal and urinary disorders Renal failure	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Renal and urinary disorders Urinary incontinence	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Reproductive system and breast disorders Breast mass	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Reproductive system and breast disorders Breast pain	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Reproductive system and breast disorders Testicular pain	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Reproductive system and breast disorders Vaginal discharge	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Reproductive system and breast disorders Vaginal hemorrhage	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Reproductive system and breast disorders Vulvovaginal burning sensation	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Choking	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Cough	44.4% 8/18 • Number of events 8 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Dysphonia	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 6/18 • Number of events 6 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Hiccups	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Lung disorder	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Nasal congestion	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Productive cough	22.2% 4/18 • Number of events 4 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Rhinalgia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Sputum discolored	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Respiratory, thoracic and mediastinal disorders Wheezing	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Acne	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Alopecia	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Dry skin	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Erythema	16.7% 3/18 • Number of events 3 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Heat rash	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Hyperhidrosis	27.8% 5/18 • Number of events 5 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Night sweats	27.8% 5/18 • Number of events 5 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Pain of skin	22.2% 4/18 • Number of events 4 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	22.2% 4/18 • Number of events 4 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Photosensitivity reaction	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Pruritus	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Rash	27.8% 5/18 • Number of events 5 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Rash macular	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Skin chapped	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Skin exfoliation	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Skin and subcutaneous tissue disorders Urticaria	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Vascular disorders Hypotension	11.1% 2/18 • Number of events 2 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Vascular disorders Hot flush	50.0% 9/18 • Number of events 9 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Vascular disorders Hypertension	55.6% 10/18 • Number of events 10 • 2 years One subject was followed for an additional 5 months until the progression of disease.
Vascular disorders Orthostatic hypotension	5.6% 1/18 • Number of events 1 • 2 years One subject was followed for an additional 5 months until the progression of disease.

Additional Information

Jane Fisher, Senior Manager, Regulatory Affairs

Jubilant Clinsys Inc.

Phone: +1 (919) 518-8786

Email: jfisher@clinsys.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place